Profiles of Circulating Exosomal Mirna in Patients with SAPHO Patients by High-Throughput Sequencing.

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disease that is characterized by autoinflammatory lesions on both bones and skin. The diverse manifestations and limited understanding of its etiology have hindered the diagnosis and treatment of this condition. SAPHO syndrome is also classified as a primary inflammatory osteitis. The onset of osteoarticular involvement in this disease is typically gradual, and the identification of associated biomarkers may be crucial for accurate diagnosis, effective treatment, and a better understanding of its underlying mechanisms. METHODS: We enrolled a total of 6 SAPHO patients and 3 healthy volunteers for this study. The miRNA expression profile in circulating exosomes was analyzed using next-generation sequencing. A total of 45 miRNAs were found to be differentially expressed in SAPHO patients. Linear discriminant analysis effect size analysis and Wilcoxon rank-sum test were employed to identify biomarkers based on these differentially expressed miRNAs. Among them, we selected 4 miRNAs as biomarkers for SAPHO syndrome, resulting in an area under the receiver operating characteristic curve of 1. RESULTS: The differentially expressed miRNAs indicated enrichment in immune system and endocrine system-related KEGG pathways, as well as infectious diseases and cancers. Furthermore, the most significantly enriched molecular functions in GO analysis were protein binding and catalytic activity. CONCLUSION: The exosomal miRNA profile in SAPHO syndrome exhibited significant changes, suggesting its potential as a candidate biomarker for diagnostic assistance, although further investigation is warranted to elucidate their role in the pathology.

Andrographolide, a natural anti-inflammatory agent: An Update.

Botanicals have attracted much attention in the field of anti-inflammatory due to their good pharmacological activity and efficacy. Andrographis paniculata is a natural plant ingredient that is widely used around the world. Andrographolide is the main active ingredient derived from Andrographis paniculata, which has a good effect on the treatment of inflammatory diseases. This article reviews the application, anti-inflammatory mechanism and molecular targets of andrographolide in different inflammatory diseases, including respiratory, digestive, immune, nervous, cardiovascular, skeletal, and tumor system diseases. And describe its toxicity and explain its safety. Studies have shown that andrographolide can be used to treat inflammatory lesions of various systemic diseases. In particular, it acts on many inflammation-related signalling pathways. The future direction of andrographolide research is also introduced, as is the recent research that indicates its potential clinical application as an anti-inflammatory agent.

High Expression Levels of SIGLEC9 Indicate Poor Outcomes of Glioma and Correlate With Immune Cell Infiltration.

Objective: This study aimed to investigate the diagnostic value and underlying mechanisms of sialic acid-binding Ig-like lectin 9 (SIGLEC9) in gliomas. Patients and Methods: The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the association of SIGLEC9 expression levels with tumor stages and survival probability. Immunohistochemical staining of SIGLEC9 and survival analysis were performed in 177 glioma patients. Furthermore, related mechanisms were discovered about SIGLEC9 in glioma tumorigenesis, and we reveal how SIGLEC9 functions in macrophages through single-cell analysis. Results: TCGA and CGGA databases indicated that patients with high SIGLEC9 expression manifested a significantly shorter survival probability than those with low SIGLEC9 expression. SIGLEC9 was upregulated significantly in malignant pathological types, such as grade III, grade IV, mesenchymal subtype, and isocitrate dehydrogenase wild-type gliomas. The immunohistochemical staining of tissue sections from 177 glioma patients showed that high-SIGLEC9-expression patients manifested a significantly shorter survival probability than low-SIGLEC9-expression patients with age ≧60 years, grade IV, glioblastoma multiforme, alpha thalassemia/intellectual disability syndrome X-linked loss, and without radiotherapy or chemotherapy. Furthermore, the SIGLEC9 expression level was positively correlated with myeloid-derived suppressor cell infiltration and neutrophil activation. The SIGLEC9 expression was also positively correlated with major immune checkpoints, such as LAIR1, HAVCR2, CD86, and LGALS9. Through single-cell analysis, we found that the SIGLEC9 gene is related to the ability of macrophages to process antigens and the proliferation of macrophages. Conclusion: These findings suggested that SIGLEC9 is a diagnostic marker of poor outcomes in glioma and might serve as a potential immunotherapy target for glioma patients in the future.

Berberine-Based Heterogeneous Linear Supramolecules Neutralized the Acute Nephrotoxicity of Aristolochic Acid by the Self-Assembly Strategy.

Aristolochic acid (AA) has been reported to cause a series of health problems, including aristolochic acid nephropathy and liver cancer. However, AA-containing herbs are highly safe in combination with berberine (Ber)-containing herbs in traditional medicine, suggesting the possible neutralizing effect of Ber on the toxicity of AA. In the present study, in vivo systematic toxicological experiments performed in zebrafish and mice showed that the supramolecule self-assembly formed by Ber and AA significantly reduced the toxicity of AA and attenuated AA-induced acute kidney injury. Ber and AA can self-assemble into linear heterogenous supramolecules (A-B) via electrostatic attraction and π-π stacking, with the hydrophobic groups outside and the hydrophilic groups inside during the drug combination practice. This self-assembly strategy may block the toxic site of AA and hinder its metabolism. Meanwhile, A-B linear supramolecules did not disrupt the homeostasis of gut microflora as AA did. RNA-sequence analysis, immunostaining, and western blot of the mice kidney also showed that A-B supramolecules almost abolished the acute nephrotoxicity of AA in the activation of the immune system and tumorigenesis-related pathways.

Long-Term Vegan Meditation Improved Human Gut Microbiota.

OBJECTIVE: Meditation has been widely used for the treatment of a variety of psychological, cardiovascular, and digestive diseases as well as chronic pain. Vegetarian diets can effectively prevent hypertension, metabolic diseases such as diabetes and obesity, and certain cancers. Meditation and vegetarian diets have been recognized as components of a healthy lifestyle and have therefore attracted more people around the world. Meditation can help regulate overall health through the neural-endocrine-immune network. Changes in dietary habits can affect the composition of the intestinal flora, which in turn affects human physiology, metabolism, nutrition, and immune function through the bacteria-intestine-brain axis. Here, we aimed to investigate the effect of long-term meditation and vegan diet on human intestinal flora. MATERIALS AND METHODS: The present study used 16S rDNA sequencing technology to detect the differences in intestinal flora between 12 healthy vegan subjects receiving long-term meditation training and 12 healthy omnivorous subjects who never received any meditation training. RESULTS: The results showed that, compared with the subjects in the omnivorous healthy control group who had never received any meditation training, the intestinal flora structure in the people who followed the long-term vegan meditation practices changed significantly. The intersection set between the results of the LEfSe analysis and the Wilcoxon rank sum test includes 14 bacterial genera. These 14 genera are defined as the dominant genera, and the AUC value was 0.92 in the ROC curve, which demonstrates that the 14 genera can be used as a biomarker to distinguish the two groups. Three beneficial bacteria genera (Bifidobacterium, Roseburia, and Subdoligranulum) were significantly enriched in the meditation group with a threshold of 4, according to the LDAs. The functional prediction of differentially enriched intestinal flora showed that the metabolism of tyrosine, propionate, niacin, and nicotinamide in the intestinal micro-organisms in the meditation group was significantly reduced compared with those in the control group, while the biosynthesis of flavones, flavone alcohols, butosin, and neomycin; flavonoid-mediated oocyte maturation; cytoskeleton protein pathways; and antigen processing and presentation were significantly enhanced. CONCLUSIONS: These results indicate that long-term vegan meditation plays a positive role in improving the body's immunity and adjusting endocrine and metabolic levels, enabling the body to be in a state of good health.

Study of the Gastrointestinal Heat Retention Syndrome in Children: From Diagnostic Model to Biological Basis.

Gastrointestinal heat retention syndrome (GHRS) refers to a condition that is associated with increased gastrointestinal heat caused by a metabolic block in energy. It is common in children and is closely related to the occurrence and development of recurrent respiratory tract infection, pneumonia, recurrent functional abdominal pain, etc. However, there are no standardized diagnostic criteria to differentiate the GHRS. Therefore, this study is aimed to establish a diagnostic model for children's GHRS and explore the possible biological basis by using systems biology to achieve. Furthermore, Delphi method and the clinical data of Lasso analysis were used to screen out the core symptoms. Nineteen core symptoms of GHRS in children were screened including digestive symptoms such as dry stool, poor appetite, vomiting, and some nervous system symptoms such as night restlessness and irritability. Based on the core symptoms, a GHRS diagnosis model was established using the eXtreme Gradient Boosting (XGBoost) method, and the accuracy of internal verification reached 93.03%. Relevant targets of the core symptoms in the Human Phenotype Ontology (HPO) were retrieved, and target interactions were linked through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and core targets were selected after topological analysis using Cytoscape. Relevant biological processes and pathways were analyzed by applying the DAVID and KEGG databases. The enriched biological processes focused on the cell proliferation, differentiation, apoptosis, and mitochondrial metabolism, which were mainly associated with PI3K-AKT, MAPK network pathways, and the Wnt signaling pathway. In conclusion, we established a diagnosis model of GHRS in children based on the core symptoms and provided an objective standard for its clinical diagnosis. And, the Wnt signaling pathway and the estrogen receptor-activated PI3K-AKT and MAPK network pathways may play important roles in the GHRS processing.